Localized Scleroderma: Predisposing and Triggering Factors

Abstract

The etiology of localized scleroderma remains unclear. The objective of this article is to review different theories of etiology, specifically provocative and predisposing factors for the development of localized scleroderma. The mini-review presents the factors, which may influence the occurrence of localized scleroderma. The genetic predisposition for the development of scleroderma is a relevant characteristic of the disease. Different traumatic factors, viral & bacterial infections, chemical substances, pharmaceutical agents may trigger localized scleroderma. Neoplasia is regarded as a distinct triggering impulse for scleroderma.

Unique Statistics:

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

The objective of this article is to summarize different theories of etiology, provocative and predisposing factors for the development of localized scleroderma, using a review of literature.

MATERIALS AND METHODS

The main source of information was Medline Pubmed including original articles, reviews, cases and clinical guidelines. The keywords “localized scleroderma” and ”etiology” were used. 360 publications from 2010 to September 2016 were analyzed. We selected 95 publications that presented the provocative & predisposing factors for localized scleroderma development.

INCLUSION AND EXCLUSION CRITERIA

The review articles, retrospective cohort studies, case series and case reports were included. The articles published before 2010 were excluded.

RESULTS

The Genetic Predisposition

On the one hand, the genetic predisposition to localized scleroderma is examined. Family cases of localized sсleroderma are known. For example, a case of localized scleroderma affecting both a father and a son was presented by Pham CM & Browning JC, (2010) [4Pham CM, Browning JC. Morphea affecting a father and son. Pediatr Dermatol 2010; 27(5): 536-7.[http://dx.doi.org/10.1111/j.1525-1470.2010.01277.x] [PMID: 21182646] ].

However, there are some reports of localized scleroderma associated with vitiligo in patients without thyroid disfunction [18Bowen C, Kobayashi TT. What is your diagnosis? Segmental vitiligo and en coup de sabre. Cutis 2010; 85(5): 230-8.[PMID: 20540411] -20Janowska M, Podolec K, Lipko-Godlewska S, Wojas-Pelc A. Coexistence of Parry-Romberg syndrome with homolateral segmental vitiligo. Postepy Dermatol Alergol 2013; 30(6): 409-11.[http://dx.doi.org/10.5114/pdia.2013.39441] [PMID: 24494006] ]. Apart from these surveys, a case of segmental vitiligo involving the left side of the trunk and left upper limb with segmental morphea involving the right side of trunk and right upper limb was present in an 18-year old girl. A history of type II diabetes mellitus in the father was elicited [21Yadav P, Garg T, Chander R, Nangia A. Segmental vitiligo with segmental morphea: An autoimmune link? Indian Dermatol Online J 2014; 5(Suppl. 1): S23-5.[http://dx.doi.org/10.4103/2229-5178.144517] [PMID: 25506558] ].

Trauma

Different physical injuries are known to be a triggering factor for scleroderma development. Arif T. & colleagues, (2015) reported a case of linear localized scleroderma in a 26-year old woman with a lesion on the frontal and forehead regions. The patient mentioned that she had had a trauma at the same site six years back [23Arif T, Majid I, Ishtiyaq Haji ML. Late onset “en coup de sabre” following trauma: rare presentation of a rare disease. Our Dermatol Online 2015; 6(1): 49-51.[http://dx.doi.org/10.7241/ourd.20151.12] ]. Trauma was the triggering factor as well in the development of linear scleroderma in a 32-year old woman. The skin lesion remained localized to the forehead during the subsequent 12 years and then the new lesions progressed down. The question of the possibility of quiescent period in the development of scleroderma was discussed [24Arif T, Majid I. Can lesions of “en coup de sabre” progress after being quiescent for a decade? Iran J Dermatol 2015; 18: 77-9.]. The cross-sectional analysis of the localized scleroderma in adults and children cohort (MAC) was performed by Grabell D & colleagues, (2014) [25Grabell D, Hsieh C, Andrew R, et al. The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the Morphea in Adults and Children cohort IV. J Am Acad Dermatol 2014; 71(3): 493-8.[http://dx.doi.org/10.1016/j.jaad.2014.04.009] [PMID: 24880663] ]. 52 (16%) among 329 patients in the MAC cohort had trauma-associated lesions at the onset of disease. Patients with lesions in an isotopic distribution had greater clinical severity as measured by a clinical outcome measure [25Grabell D, Hsieh C, Andrew R, et al. The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the Morphea in Adults and Children cohort IV. J Am Acad Dermatol 2014; 71(3): 493-8.[http://dx.doi.org/10.1016/j.jaad.2014.04.009] [PMID: 24880663] ]. Another cross-sectional survey of the MAC cohort emphasized the role of skin trauma [26Wolf R, Wolf D, Ruocco V, Ruocco E. The role of skin trauma (isotopic and isomorphic) in the distribution of morphea. J Am Acad Dermatol 2015; 72(3): 560-1.[http://dx.doi.org/10.1016/j.jaad.2014.10.046] [PMID: 25687315] ]. The mechanical compression from clothes [27Arif T, Hassan I, Anwar P, Amin SS. Slim belt induced morphea. Price paid for a slimmer look. Our Dermatol Online 2015; 6(3): 347-9.[http://dx.doi.org/10.7241/ourd.20153.93] ], particularly slim belt, is discussed [27Arif T, Hassan I, Anwar P, Amin SS. Slim belt induced morphea. Price paid for a slimmer look. Our Dermatol Online 2015; 6(3): 347-9.[http://dx.doi.org/10.7241/ourd.20153.93] ]. The appearance of localized scleroderma lesions after fluoroscopy, laparotomy and rhinoplasty was outlined [28Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol 2015; 90(1): 62-73.[http://dx.doi.org/10.1590/abd1806-4841.20152890] [PMID: 25672301] -30Fett N, Werth VP. Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol 2011; 64(2): 217-28.[http://dx.doi.org/10.1016/j.jaad.2010.05.045] [PMID: 21238823] ].

DISCUSSION

The genetic predisposition to localized scleroderma has been investigated in the recent years [4Pham CM, Browning JC. Morphea affecting a father and son. Pediatr Dermatol 2010; 27(5): 536-7.[http://dx.doi.org/10.1111/j.1525-1470.2010.01277.x] [PMID: 21182646] -8Jacobe H, Ahn C, Arnett FC, Reveille JD. Major histocompatibility complex class I and class II alleles may confer susceptibility to or protection against morphea: findings from the Morphea in Adults and Children cohort. Arthritis Rheumatol 2014; 66(11): 3170-7.[http://dx.doi.org/10.1002/art.38814] [PMID: 25223600] ]. The triggering factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis [95Kreuter A. Localized scleroderma. Dermatol Ther (Heidelb) 2012; 25(2): 135-47.[http://dx.doi.org/10.1111/j.1529-8019.2012.01479.x] [PMID: 22741933] ]. Actually, there are no obligatory triggering factors, but each group of them can be crucial for a certain group of patients.

Endorsements

"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."

Daniel Pesut(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."

Patrice Talaga(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."

Jeffrey M. Weinberg(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."

Debomoy K. Lahiri(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."

Robert Looney(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."

Richard Reithinger(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."

J. Ferwerda(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."

Sean L. Kitson(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."

Hubert Wolterbeek(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."

Alessandro Laviano(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."

Philippe Hernigou(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."

M. Bendandi(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."

Peter Chiba(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."

Jaime Sampaio(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."

Eduardo A. Castro(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."

Kenji Hashimoto(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."

Daniel Shek(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."